Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population.

Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10-15 and 4.84 × 10-10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10-4, and 7.15 × 10-4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10-8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351-1.700), 1.43 × 10-12 and MD-MAFLD: 1.300 (1.191-1.416), 2.90 × 10-9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10-8 and 1.225 (1.122, 1.340), 7.06 × 10-6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

The relationship between metabolic dysfunction-associated fatty liver disease and low muscle mass in an asymptomatic Korean population.

BACKGROUND: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) emphasizes the metabolic dysfunction in nonalcoholic fatty liver disease (NAFLD). Although the relationship between low muscle mass and NAFLD has been suggested, the effect of MAFLD on low muscle mass is yet to be investigated. In this study, we examined the relationship between MAFLD and low muscle mass in an asymptomatic Korean population. METHODS: Examinees who underwent FibroScan® and bioelectrical impedance analyses on the same day during the period of June 2017 to December 2019 were included. Hepatic steatosis was diagnosed using controlled attenuation parameter (CAP) with two cut-off values of 248 and 294 dB/m. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight (wt) or body mass index (BMI) ratios of two standard deviations below the sex-specific mean for healthy young adults. Subjects were divided into four subgroups: diabetic MAFLD (presence of diabetes mellitus [DM]), metabolic dysfunction (MD) MAFLD (≥2 metabolic abnormalities without DM), overweight MAFLD (overweight/obese without DM and <2 metabolic abnormalities) and no MAFLD. RESULTS: Among all of the 6414 subjects (mean 53.9 years of age; 85.4% male), the prevalence of MAFLD was 49.9% and 22.7% for CAP cut-off values of 248 and 294 dB/m, respectively. In the multivariate analysis, MAFLD was associated with an increased risk of both low muscle mass_wt (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.38-2.35, P < 0.001) and low muscle mass_BMI (OR 1.31, 95% CI 1.01-1.70, P = 0.042). The risk of low muscle mass_wt and low muscle mass_BMI increased the most in the diabetic MAFLD subgroup compared with the no-MAFLD group (OR 2.11, 95% CI 1.51-2.96, P < 0.001 and OR 1.51, 95% CI 1.08-2.13, P = 0.017). There was an increased risk of low muscle mass_wt in the MD MAFLD subgroup (OR 1.73, 95% CI 1.31-2.28, P < 0.001). Comparable results were observed when the CAP cut-off value of 294 dB/m was applied. CONCLUSIONS: The presence of MAFLD is significantly associated with increased risk of low muscle mass with varying risks according to the MAFLD subgroups. Clinicians should be aware of the differentiated risk of low muscle mass across the subgroups of MAFLD.

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology.

BACKGROUND: Helicobacter pylori (H. pylori) infection is known to prevent the occurrence of gastroesophageal reflux disease (GERD) by inducing gastric mucosal atrophy. However, little is known about the relationship between atrophic gastritis (AG) and GERD. AIM: To confirm the inverse correlation between AG and the occurrence and severity of GERD. METHODS: Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included. The grade of reflux esophagitis was evaluated according to the Los Angeles classification. Endoscopic AG (EAG) was categorized into six grades. Serologic AG (SAG) was defined as pepsinogen I ≤ 70 ng/mL and pepsinogen I/II ratio ≤ 3.0. The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis. RESULTS: In total, 4684 individuals with GERD were compared with 21901 healthy controls. In multivariate logistic regression analysis, advanced age, male sex, body mass index > 23 kg/m2, presence of metabolic syndrome, current smoking, and alcohol consumption were associated with an increased risk of GERD. Seropositivity for H. pylori immunoglobulin G antibodies was associated with a decreased risk of GERD. There was an inverse correlation between the extent of EAG and occurrence of GERD: Odds ratio (OR), 1.01 [95% confidence interval (CI): 0.90-1.14] in C1, 0.87 (0.78-0.97) in C2, 0.71 (0.62-0.80) in C3, 0.52 (0.44-0.61) in O1, 0.37 (0.29-0.48) in O2, and 0.28 (0.18-0.43) in O3. Additionally, the extent of EAG showed an inverse correlation with the severity of GERD. The presence of SAG was correlated with a reduced risk of GERD (OR = 0.49, 95%CI: 0.28-0.87, P = 0.014). CONCLUSION: The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD. AG followed by H. pylori infection may be independently protect against GERD.

Impact of comprehensive optical diagnosis training using Workgroup serrAted polypS and Polyposis classification on detection of adenoma and sessile serrated lesion.

OBJECTIVES: Many interventions have been attempted to improve adenoma detection rate (ADR) and sessile serrated lesion detection rate (SDR), and one of these interventions is educational training to recognize polyp characteristics. This study aimed to investigate the change in polyp detection rates of endoscopists before and after comprehensive training through the Gangnam-Real Time Optical Diagnosis (Gangnam-READI) program. METHODS: Fifteen gastroenterologists participated in a 1-year comprehensive training program that consisted of ex vivo and in vivo training that encompasses knowledge and skills in endoscopic characterization of colonic polyps using the Workgroup serrAted polypS and Polyposis (WASP) classification. We evaluated the impact of the training program by comparing the overall and individual ADR and SDR 6 months before and after the training. RESULTS: Overall, 18,280 polyps (9337 adenomas and 855 sessile serrated lesion) were collected. The optical diagnosis training had no significant impact on the difference in ADR after training compared to before training (47.7% vs. 46.5%, P = 0.608). A tendency for a decrease in ADR variance was noted among the endoscopists after training (74.9 vs. 32.7, P = 0.121). The overall pre-training period SDR was 4.5% and showed a statistically significant increase to 5.6%, 8.0%, and 7.1% in the first and second half of the training period, and post-training period, respectively (P = 0.003). The optical diagnosis training did not decrease variance in SDR (8.9 vs. 8.8, P = 0.985). CONCLUSION: Comprehensive optical diagnosis training with WASP classification has a significant impact on increasing the overall SDR of expert endoscopists.

The association between Helicobacter pylori with nonalcoholic fatty liver disease assessed by controlled attenuation parameter and other metabolic factors.

AIM: Existing studies have suggested an association between Helicobacter pylori (Hp) infection and nonalcoholic fatty liver disease (NAFLD). We investigated the relationship between Hp infection and NAFLD using controlled attenuation parameter (CAP) and other metabolic factors. METHOD: We conducted a retrospective cohort study of apparently healthy individuals who underwent liver Fibroscan during health screening tests between January 2018 and December 2018. Diagnosis of Hp infection was based on a serum anti-Hp IgG antibody test and CAP values were used to diagnose NAFLD. RESULTS: Among the 1,784 subjects (mean age 55.3 years, 83.1% male), 708 (39.7%) subjects showed positive results of Hp serology. In the multivariate analysis, obesity (body mass index ≥25) (odds ratio [OR] 3.44, 95% confidence interval [CI] 2.75-4.29), triglyceride (OR 2.31, 95% CI 1.80-2.97), and the highest tertile of liver stiffness measurement (OR 2.08, 95% CI 1.59-2.71) were found to be associated with NAFLD, defined by CAP ≥248 dB/m, while Hp-seropositivity showed no association with NAFLD. Serum levels of HDL cholesterol significantly decreased in subjects with Hp-seropositivity compared to HP-seronegativity in both groups with and without NAFLD (P<0.001). CONCLUSION: While Hp seropositivity was not associated with CAP-defined NAFLD, serum HDL cholesterol level were negatively associated with Hp-seropositivity in both groups with and without NAFLD. Further clinical and experimental studies are necessary to determine the association between Hp infection and NAFLD.

Fatty Liver Index for Predicting Nonalcoholic Fatty Liver Disease in an Asymptomatic Korean Population.

Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, highlighting the importance of early and accurate detection and the appropriate management of NAFLD. However, ultrasonography (US) is not included in many mass screening programs, and people have limited access to it. The aim of this study is to validate the fatty liver index (FLI) and investigate the optimal cutoff value for predicting NAFLD in an asymptomatic population. We conducted a retrospective cohort study in Korea. All subjects who underwent health checkup exams, including abdominal US, controlled attenuation parameter (CAP) and blood testing, were enrolled. Analyses of the area under the receiver operating characteristic curve (AUROC) were used to evaluate the diagnostic accuracy and to calculate the optimal FLI cutoff for US-NAFLD. Among the 4009 subjects (mean age 54.9 years, 83.5% male), the prevalence of US-diagnosed NAFLD and CAP-defined hepatic steatosis was 61.4% and 55.4%. The previously used cutoff of FLI = 60 showed poor performance in predicting US-diagnosed NAFLD, with an AUROC of 0.63 (0.62-0.64), and CAP-defined NAFLD, with an AUROC 0.63 (0.62-0.64). The optimal FLI cutoff values to discriminate fatty liver detected by US were 29 for the entire population, with an AUROC of 0.82 (0.81-0.84). The sex-specific values were 31 for males and 18 for females (sensitivity 72.8% and 73.4%; specificity 74.2% and 85.0%, respectively). The FLI cutoff for US-diagnosed NAFLD can be set as 29 for the entire Korean population. Considering the sex dimorphism in NAFLD, different cutoff values are suggested to predict US-diagnosed NAFLD. These results may be helpful in the accurate non-invasive diagnosis of NAFLD.

The Risk of Colorectal Adenoma in Nonalcoholic or Metabolic-Associated Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease associated with various metabolic disorders. Metabolic dysfunction-associated fatty liver disease (MAFLD) emphasizes metabolic dysfunction in NAFLD. Although the relationship between NAFLD and colorectal adenomas has been suggested, the effect of MAFLD on colorectal adenoma has yet to be investigated. In this study, we examined the relationship between NAFLD/MAFLD and colorectal adenoma in comparison with other metabolic factors. METHODS: Examinees who underwent colonoscopy and abdominal ultrasonography on the same day from January 2012 to December 2012 were included. NAFLD was diagnosed according to the findings of ultrasonography. The Fibrosis-4 (FIB-4) index was used as a surrogate marker for advanced hepatic fibrosis. A logistic regression model was used to analyze the risk of NAFLD/MAFLD for colorectal adenoma. RESULTS: The prevalence of NAFLD and MAFLD was 37.5% and 32.8%, respectively. In the multivariate analysis, male sex, older age, diabetes, and smoking increased the risk of colorectal adenoma. NAFLD and MAFLD were the most important risk factors for colorectal adenoma only in females [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.01-2.03, and OR 1.55, 95% CI 1.09-2.20, respectively]. NAFLD and MAFLD with an advanced fibrosis index were significantly associated with an increased risk of colorectal adenoma. (NAFLD: OR 1.38, 95% CI, 1.04-1.83, p = 0.027; MAFLD: OR 1.45, 95% CI, 1.13-1.96, p = 0.004, respectively). CONCLUSION: NAFLD and MAFLD were significantly associated with a higher risk of colorectal adenomas, especially in females. NAFLD and MAFLD with advanced fibrosis were associated with an increased risk of colorectal adenoma. Colonoscopic examinations may be emphasized for patients with NAFLD/MAFLD, for women, or patients with the presence of hepatic fibrosis.

Hepatic fibrosis is associated with an increased rate of decline in bone mineral density in men with nonalcoholic fatty liver disease.

BACKGROUND: There is still controversy about the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). The aim of this study was to clarify the association between NAFLD and the decline in BMD in healthcare examinees. METHODS: Participants who underwent regular health check-ups with BMD and hepatic ultrasonography from 2006 to 2015 with more than one follow-up until 2020 were included. Propensity score matching was performed between the NAFLD group and the control group, and mixed linear regression models were used for the longitudinal analysis. RESULTS: Of 2623 eligible participants (mean age 58.7 ± 7.3 years; males 31.3%), 888 (33.9%) had NAFLD. At baseline, the NAFLD group had a higher total hip BMD than the non-NAFLD group in men (0.988 vs. 1.015 g/cm2, p = 0.007); however, there was no difference in baseline BMD in women (p = 0.253). In longitudinal analysis during a follow-up period of 7.1 years, there was no significant difference in the BMD decline rate between the two groups in the PS-matched cohort (p = 0.816 in men and p = 0.827 in women). However, among men with NAFLD, those with a high and intermediate probability of advanced fibrosis by the FIB-4 showed a significantly increased rate of decline in total hip BMD compared to those with low scores (0.01 vs. - 0.19% change/year, p = 0.011). CONCLUSIONS: NAFLD was not associated with the total hip BMD decline rate. However, hepatic fibrosis was significantly associated with an increased rate of decline in total hip BMD in men with NAFLD. CLINICAL TRIAL REGISTRATION: This study is a retrospective observational study and is not a drug trial. There was no need for clinical trial registration.

The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea.

BACKGROUND: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). METHODS: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. RESULTS: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38-2.78; class II, OR: 3.33, 95% CI: 1.77-6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31-2.95; class II, OR: 2.96, 95% CI: 1.51-5.78). CONCLUSION: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.

Body weight gain rather than body weight variability associated with increased risk of nonalcoholic fatty liver disease.

Weight loss, the most established therapy for nonalcoholic fatty liver disease (NAFLD), is frequently followed by weight regain and fluctuation. The aim of this study was to investigate whether body weight change and variability were independent risk factors for incident NAFLD. We conducted a longitudinal cohort study. Among the 1907 participants, incident NAFLD occurred in 420 (22.0%) cases during median follow-up of 5.6 years. In the multivariate analysis, there was no significant association between weight variability and the risk of incident NAFLD. The risk of incident NAFLD was significantly higher in subjects with weight gain ≥ 10% and 7% < gain ≤ 10% [hazard ratios (HR), 2.43; 95% confidence intervals (CI), 1.65-3.58 and HR, 1.73; 95% CI, 1.26-2.39, respectively], while the risk of incident NAFLD was significantly lower in those with -7% < weight loss ≤ --3% (HR, 0.33; 95% CI, 0.22-0.51). Overall body weight gain rather than bodyweight variability was independently associated with the risk of incident NAFLD. Understanding the association between body weight variability and incident NAFLD may have future clinical implications for the quantification of weight loss as a treatment for patients with NAFLD.

The Association between Vitamin D and Nonalcoholic Fatty Liver Disease Assessed by Controlled Attenuation Parameter.

BACKGROUND: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). METHODS: We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. RESULTS: Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47-1.00 in Q2 vs. Q1; OR 0.65, 95% CI 0.44-0.94 in Q3 vs. Q1; and OR 0.64, 95% CI 0.44-0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31-0.87 in Q4 vs. Q1). CONCLUSIONS: Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.

Nonalcoholic Fatty Liver Disease Is Associated with Benign Prostate Hyperplasia.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with a wide spectrum of metabolic abnormalities. This study aimed to evaluate whether NAFLD is associated with benign prostatic hyperplasia (BPH) independent of other risk factors. METHODS: A total of 3,508 subjects who underwent prostate and hepatic ultrasonography were enrolled. NAFLD was diagnosed and graded by ultrasonographic findings. BPH was defined by total prostate volume. RESULTS: The prevalence of BPH was significantly increased according to NAFLD severity (P < 0.001). The multivariate analysis showed that NAFLD was associated with a 22% increase in the risk of BPH (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02-1.45). In non-obese subjects, NAFLD was associated with a 41% increase in the risk of BPH (OR, 1.41; 95% CI, 1.14-1.73), and an incremental increase in the risk of BPH according to NAFLD severity was pronounced (adjusted OR [95% CI], 1.32 [1.05-1.68] for mild NAFLD, 1.55 [1.15-2.10] for moderate to severe NAFLD vs. no NAFLD, P for trend = 0.004). However, in the obese population, the association of NAFLD in the risk of BPH was insignificant (P = 0.208). CONCLUSION: NAFLD is associated with an increased risk of BPH regardless of metabolic syndrome, especially in non-obese subjects. An incrementally increased risk of BPH according to NAFLD severity is prominent in non-obese subjects with NAFLD. Thus, physicians caring for non-obese patients with NAFLD may consider assessing the risk of BPH and associated urologic conditions.

Improved Accuracy in Optical Diagnosis of Colorectal Polyps Using Convolutional Neural Networks with Visual Explanations.

BACKGROUND & AIMS: Narrow-band imaging (NBI) can be used to determine whether colorectal polyps are adenomatous or hyperplastic. We investigated whether an artificial intelligence (AI) system can increase the accuracy of characterizations of polyps by endoscopists of different skill levels. METHODS: We developed convolutional neural networks (CNNs) for evaluation of diminutive colorectal polyps, based on efficient neural architecture searches via parameter sharing with augmentation using NBIs of diminutive (≤5 mm) polyps, collected from October 2015 through October 2017 at the Seoul National University Hospital, Healthcare System Gangnam Center (training set). We trained the CNN using images from 1100 adenomatous polyps and 1050 hyperplastic polyps from 1379 patients. We then tested the system using 300 images of 180 adenomatous polyps and 120 hyperplastic polyps, obtained from January 2018 to May 2019. We compared the accuracy of 22 endoscopists of different skill levels (7 novices, 4 experts, and 11 NBI-trained experts) vs the CNN in evaluation of images (adenomatous vs hyperplastic) from 180 adenomatous and 120 hyperplastic polyps. The endoscopists then evaluated the polyp images with knowledge of the CNN-processed results. We conducted mixed-effect logistic and linear regression analyses to determine the effects of AI assistance on the accuracy of analysis of diminutive colorectal polyps by endoscopists (primary outcome). RESULTS: The CNN distinguished adenomatous vs hyperplastic diminutive polyps with 86.7% accuracy, based on histologic analysis as the reference standard. Endoscopists distinguished adenomatous vs hyperplastic diminutive polyps with 82.5% overall accuracy (novices, 73.8% accuracy; experts, 83.8% accuracy; and NBI-trained experts, 87.6% accuracy). With knowledge of the CNN-processed results, the overall accuracy of the endoscopists increased to 88.5% (P < .05). With knowledge of the CNN-processed results, the accuracy of novice endoscopists increased to 85.6% (P < .05). The CNN-processed results significantly reduced endoscopist time of diagnosis (from 3.92 to 3.37 seconds per polyp, P = .042). CONCLUSIONS: We developed a CNN that significantly increases the accuracy of evaluation of diminutive colorectal polyps (as adenomatous vs hyperplastic) and reduces the time of diagnosis by endoscopists. This AI assistance system significantly increased the accuracy of analysis by novice endoscopists, who achieved near-expert levels of accuracy without extra training. The CNN assistance system can reduce the skill-level dependence of endoscopists and costs.

A genome-wide association study on liver enzymes in Korean population.

BACKGROUND: Although genetic features vary across ethnicities, few genome-wide association studies (GWAS) have reported the genetic determinants of liver enzyme expression. This study was aimed to evaluate the associations of genome-wide single nuclear polymorphisms (SNPs) with the liver enzymes in a Korean population. METHODS: We performed a GWAS to identify genetic loci influencing liver function, as measured by concentrations of alkaline phosphatase (ALP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) in in Korean study participants. RESULTS: A total of 6,488 subjects (4,457 in the discovery and 2,031 in the validation set) were included. The mean subject age was 50.0±10.6 years (male, 53.7%). Among a total of 546,738 SNPs tested, rs651007 and rs579459 located in the ABO gene showed strong associations with ALP (P = 1.63×10-8 and 5.61×10-8, respectively [discovery set]; P = 4.08×10-15 and 9.92×10-16, respectively [validation set]). Additionally, rs5751901 and rs2006092, which are located in the GGT1 gene, showed strong associations with GGT (P = 6.44×10-15 and 1.26×10-15, respectively [discovery set]; P = 4.13×10-10 and 5.15×10-11, respectively [validation set]). Among the 13 SNPs that showed genome-wide significance with total bilirubin levels, rs10929302 and rs6742078 showed the most significant association (P = 3.08×10-64 and 2.05×10-62, respectively [discovery set]; P = 1.33×10-116 and 2.24×10-118, respectively [validation set]). No genome-wide significant associations was found for ALT. CONCLUSIONS: We demonstrated that ABO, GGT1 and UGT1A family were associated with ALP, GGT and BIL, respectively in Korean population. These findings differ from reported results in GWAS in European populations in terms of associated genes and locations, suggesting different genetic mechanisms of liver enzyme regulation according to ethnicity.

Association Between Anxiety and Depression and Nonalcoholic Fatty Liver Disease.

Backgrounds: Depression and anxiety disorder are frequently seen in patients with nonalcoholic fatty liver disease (NAFLD). However, the associations between mood disorders and NAFLD have not been fully evaluated. In this study, we investigated the relationship between NAFLD and depression or anxiety in a Korean population. Methods: We conducted a retrospective cross-sectional study that included subjects who underwent abdominal ultrasonography and completed a symptom questionnaire for a routine health check-up. NAFLD was diagnosed and graded according to the ultrasonography findings. Depression and anxiety were assessed using the Beck Depression Inventory and State-Trait Anxiety Inventory, respectively. Results: Among the total of 25,333 subjects, the mean age was 47 years (men, 56.2%), and the prevalence rate of NAFLD was 30.9%. In the multivariate analysis, NAFLD showed a significant association with depression [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.14-1.80, p = 0.002] in women. Severe NAFLD significantly correlated with state anxiety and trait anxiety (adjusted OR 1.84 and 95% CI 1.01-3.37, p = 0.047 and adjusted OR 2.45 and 95% CI 1.08-4.85, p = 0.018, respectively) in women. Conclusions: There was a higher tendency of women with NAFLD to suffer from depression with increase in steatosis, and severe stage of steatosis was significantly associated with anxiety in the female compared to non-NAFLD. Understanding the association between NAFLD and mood disorders may have clinical implications for reducing the prevalence of comorbidities.

Multidirectional Colonoscopy Quality Improvement Increases Adenoma Detection Rate: Results of the Seoul National University Hospital Healthcare System Gangnam Center Colonoscopy Quality Upgrade Project (Gangnam-CUP).

BACKGROUND: To prevent colorectal cancer, high-quality colonoscopy is advocated, undertaken by endoscopists with high adenoma detection rates (ADRs). Despite reports that various factors may impact ADRs, the significance of such factors is still unclear. AIMS: The analysis was aimed at quality-oriented interventions for boosting ADRs. METHODS: Study enrollees were adults subjected to screening colonoscopy between September 2013 and August 2016 at the Gangnam Center of Seoul National University Hospital Healthcare System. The investigation entailed six periods (P1-6) of 6 months each, during which serial multidirectional quality improvement efforts were instituted. In particular, we sought to further educate endoscopists, provide feedback on individual ADRs, and introduce a split-dose regimen, gauging results via the Boston Bowel Preparation Score. Changes in polyp detection rates (PDRs) and ADRs were then analyzed. RESULTS: A total of 13,430 colonoscopies were undertaken by 15 experienced endoscopists. Overall, the ADR increased from 45.6% (P1) to 48.2% (P6, p < 0.001). The PDR, ADR, and advanced adenoma detection rate (AdvADR) showed the greatest increases between P3 and P4 [PDR 67.8% → 71.2% (p < 0.001); ADR 44.1% → 47.7% (p = 0.001); AdvADR 2.3% → 3.3% (p = 0.028)] in keeping with the introduction of a split-dose regimen. The sessile serrated adenoma detection rate (SSADR) increased substantially from 2.1% (P1) to 7.9% (P6, p < 0.001), with the largest gain between P1 and P2, just after education (p = 0.023). CONCLUSIONS: Successful quality improvement in colonoscopy was achieved through comprehensive multidirectional efforts in education, feedback, and enhanced bowel preparation. Achieving high-level bowel preparation was paramount in ADR improvement. The SSADR was improved through education.

Long-term outcomes of HBsAg/anti-HBs double-positive versus HBsAg single-positive patients with chronic hepatitis B.

The coexistence of HBsAg and anti-HBs has been reported in some chronic hepatitis B patients; however, the long-term outcomes of this serological profile have not been elucidated. We aimed to evaluate the long-term outcomes of HBsAg/anti-HBs double-positive chronic hepatitis B patients. Chronic hepatitis B patients who underwent baseline abdominal ultrasonography and follow-up (HBsAg/anti-HBs assessment and abdominal ultrasonography) at our healthcare center were included. The "coexistence group" included patients positive for both HBsAg and anti-HBs and the "control group" included patients positive for only HBsAg during follow-up. The outcomes were hepatocellular carcinoma (HCC) incidence, HBsAg seroclearance and overall mortality. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Of the 2,341 eligible patients, 166 (7.1%) were in the coexistence group. The total follow-up duration was 5.4 years. The coexistence group had a 3.08-fold higher risk of HCC than the control group [hazard ratio (HR) 3.08, 95% confidence interval(CI) 1.26-7.55, P = 0.014] in multivariate analysis. The coexistence group had more HBsAg seroclearance than the control group (HR 1.43, 95% CI 1.01-2.03, P = 0.046). However, overall mortality did not significantly differ between the 2 groups. The coexistence group is heterogeneous and includes subjects with unfavorable outcomes (incidence of HCC) and favorable outcomes (more HBsAg seroclearance).

Improved Real-Time Optical Diagnosis of Colorectal Polyps Following a Comprehensive Training Program.

BACKGROUND & AIMS: The optimal training method for endoscopic characterization of colorectal polyps using narrow-band imaging is uncertain, and sessile serrated lesions (SSLs) optical diagnosis data are lacking. We aimed to evaluate a comprehensive training program for real-time optical diagnosis of colorectal polyps, including SSLs. METHODS: We performed a single-institution prospective study of 15 endoscopists trained with the Workgroup Serrated Polyps and Polyposis classification system. After the first phase of in vivo optical diagnosis, their performances were evaluated. After re-education for insufficient competency, they began the second phase. The learning curves and performance on 2 preservation and incorporation of valuable endoscopic innovations benchmarks were assessed. RESULTS: A total of 7294 polyps, including 486 SSLs, were diagnosed in real-time. The overall accuracy improved from 73.5% in the first phase to 77.1% in the second. The accuracy with high confidence was 79.4% and 85.1% in the first and second phases, respectively. In the first and second phases, the negative predictive values for diminutive neoplastic polyps were 82.1% and 92.5%, respectively, and concordances of the surveillance intervals were 80.7% and 89.7%, respectively. Eight endoscopists achieved the preservation and incorporation of valuable endoscopic innovations benchmarks after the second phase compared with none after the first. In contrast, the high confidence rate decreased from 74.6% to 70.2% as training progressed. CONCLUSION: A comprehensive training program for real-time optical diagnosis significantly improved performance and reduced individual variability in less-experienced endoscopists. ClinicalTrials.gov no: NCT02516748.

Nonalcoholic fatty liver disease is associated with breast cancer in nonobese women.

BACKGROUND: Growing evidence supports that nonalcoholic fatty liver disease (NAFLD) is associated with extrahepatic cancers. Nonalcoholic fatty liver disease (NAFLD) and breast cancer share similar risk factors, including obesity. AIM: The aim of this case-control study was to investigate the association between NAFLD and breast cancer. METHODS: Subjects who received health screening, including mammography and breast and hepatic ultrasonography simultaneously, were included. Subjects diagnosed with breast cancer were matched with controls. Conditional logistic regression analyses were performed. RESULTS: Among 270 breast cancer patients and 270 controls, 81 cancer patients (30.0%) and 54 controls (20.0%) had NAFLD (P = 0.008). NAFLD was significantly associated with breast cancer in multivariate analysis (P = 0.046). When the interaction between obesity (BMI < 25 kg/m2 vs. ≥25 kg/m2) and NAFLD in breast cancer patients was examined, a significant effect modification between obesity and NAFLD in breast cancer was noted (P = 0.021). The subgroup analysis showed that NAFLD was significantly associated with breast cancer in the nonobese subgroup (odds ratio 3.04, 95% confidence interval 1.37-4.32, P = 0.002) but not in the obese group (P = 0.163). CONCLUSIONS: NAFLD was significantly associated with breast cancer independent of traditional risk factors, and this association existed in the nonobese subgroup but not in the obese subgroup.